Simple UV and visible spectrophotometric methods for the determination of doxycycline hyclate in pharmaceuticals

Doxycycline hyclate (DOX), a broad spectrum antibiotic with activity against a wide range of gram-positive and gram-negative bacteria, is widely used as a pharmacological agent and as an effector molecule in inducible gene expression system. Three simple, selective, rapid, accurate, precise and cost-effective spectrophotometric methods for the determination of DOX in bulk drug and in tablets have been developed and validated. First method (method A) is based on the measurement of absorbance of DOX in 0.1 M HCl at 240 nm. The second method (method B) is based on the measurement of yellow chromogen at 375 nm which is formed in 0.1 M NaOH. The third method is based on the measurement of 2: 1 complex formed between DOX and iron(III) in H₂SO₄ medium, the complex peaking at 420 nm (method C). The optimum conditions for all the three methods are optimized. Beer’s law was obeyed over the ranges 2.5–50.0, 1.50–30.0 and 10–100 g/mL for method A, method B and method C, respectively. The apparent molar absorptivity values are calculated to be 1.03 × 10⁴, 1.73 × 10⁴, and 5.21 × 10³ L mol⁻¹ cm⁻¹ for method A, method B, and method C, respectively. The Sandell sensitivity, limit of detection (LOD) and limit quantification (LOQ) values are also reported. All the methods were validated in accordance with current ICH guidelines. The developed methods were employed with high degree of precision and accuracy for the estimation of total drug content in commercial tablet formulations of DOX.     

Non-aqueous and two-phase titrimetric assay of isoxsuprine hydrochloride in pharmaceuticals

Based on the nitrogenous base or quaternary ammonium moiety in isoxsuprine hydrochloride (ISX), two highly accurate and selective titrimetric methods are proposed f or the determination of ISX in spiked human urine, injection and tablets. Non-aqueous titration (Method A) involves removal of protonated amine using mercuric acetate for enhanced basic nitrogen prior to titration with perchloric acid in an acetic acid medium using crystal violet as indicator. Two-phase titration (Method B) is based on ion association complex formation between sodium lauryl sulphate (SLS) and protonated amine of ISX at pH 2.5 in aqueous phase, end point being detected by change in dimethyl yellow color in chloroform layer. The methods are applicable over the concentration range 2.0–20.0 mg and 1.0–10.0 mg for method A and method B, respectively. Calculations are based on 1: 1 molar ratio, i.e., JSX: HClO₄ for method A and ISX: SLS for method B, owing to the presence of one nitrogen atom. Method A is applicable to the determination of ISX in tablets whereas method B is applicable to spiked human urine, injection and tablets. The methods are validated statistically by comparing the results with those of the reference method by applying the Student’s t-test and F-test. The accuracy was further ascertained by recovery studies via standard addition technique.     

Use of an oxidation reaction for the quantitative determination of albendazole with Chloramine-T and acid dyes.

One titrimetric and two spectrophotometric procedures have been reported for the determination of albendazole and its tablets. Using titrimetry, the drug was titrated directly with Chloramine-T under acidic conditions using a Methyl Orange indicator. The spectrophotometric procedures involve treating the sample solution with a measured excess of Chloramine-T in an acid medium, followed by an estimation of unreacted Chloramine-T by reacting with a fixed amount of either Methyl Orange or Indigo Carmine dye solution and measuring the absorbance at 510 nm or 610 nm. The stoichiometric ratio, which forms the basis for the calculations in titrimetry as well as the range of the applicability, are reported. The Beer's law range and sensitivity values for spectrophotometric procedures are included. The methods were applied to the determination of albendazole in tablets with satisfactory results.     

Titrimetric and spectrophotometric assay of pantoprazole in pharmaceuticals using cerium(IV) sulphate as oxidimetric agent

Titrimetric and spectrophotometric assay of pantoprazole sodium sesquihydrate (PSS) using cerium(IV) sulphate as the oxidimetric reagent is described. The methods are based on the oxidation of PSS with a measured excess of Ce(IV) sulphate followed by the determination of unreacted oxidant using different reaction schemes. In titrimetry, the unreacted oxidant was determined by back titration with ferrous ammonium sulphate (FAS) in sulphuric acid medium. Spectrophotometry involves the reduction of unreacted Ce(IV) sulphate with a fixed quantity of Fe(II). The resulting Fe(III) is complexed with thiocyanate and the absorbance is measured at 470 nm. In both the methods, the amount of Ce(lV) sulphate reacted corresponds to PSS concentration. Titrimetry is applicable over 1–10 mg range whereas in spectrophotometry, the calibration graph is linear in the range of 0.5–7.0 μg/mL and the calculated molar absorptivity value is 1.58 × 10⁵ L/mol cm. The validity of the proposed methods was tested by analyzing pure and dosage forms containing PSS. Statistical treatment of the results reflects that the proposed procedures are precise, accurate and easily applicable to the determination of PSS in pure form and in pharmaceutical formulations.     

Quantitative determination of lansoprozole in capsules and spiked human urine by spectrophotometry through ion-pair complex formation reaction

Two simple, rapid and sensitive extraction-free spectrophotometric methods are proposed for the determination of lansoprazole (LAN) in bulk drug and in its capsule formulation. The methods are based on the interaction of LAN in dichloromethane (DCM) with acidic sulfonphthalein dyes, namely, bromocresol purple (BCP) in method A and bromothylmol blue (BTB) in method B to form stable, yellow-colored, ion-pair complexes peaking at 400 and 430 nm, respectively. The parameters that affect the reaction were carefully optimized, and under the optimized conditions, linear relationships were obtained in the ranges of 0.5–15.0 and 1.25–20.0 μg mL^?1 LAN for method A and method B, respectively. The molar absorptivity values are calculated to be 2.10 × 10⁴ and 1.50 × 10⁴ L mol^?1 cm^?1 for method A and method B, respectively. The composition of the ion-pairs was found to be 1:1 by Job’s method of continuous variations and the conditional stability constant (log K_f) of the complexes has been calculated. The proposed methods were applied successfully to the determination of LAN in capsules as well as in spiked urine sample with good accuracy and precision. The results obtained by the proposed methods were compared favorably with those of the reference method.     

Titrimetric and Spectrophotometric Determination of Some Phenothiazine Psychotropics in Pure Form and in Pharmaceutical Formulations with Metavanadate

 Two simple, fast, accurate and precise methods for the determination of six phenothiazines and a number of their pharmaceutical formulations are described. The titrimetric method involves the oxidation of the drugs by metavanadate in sulphuric acid medium and titration of vanadium(IV) formed, with cerium(IV) using ferroin indicator and acetone as catalyst. In spectrophotometry, vanadium(IV) formed was reacted with ferriin and the resulting ferroin measured at 510 nm. Phenothiazines in the ranges 5–100 mg and 2.5–25.0 μg mL⁻¹ can be determined by titrimetry and spectrophotometry, respectively, with detection limits of 0.96–2.05 mg and 0.0359–0.0565 μg mL⁻¹, respectively. Both methods were applied successfully to the determination of the studied drugs in pharmaceutical preparations. The reliability of the assays was established by parallel determination by the official methods of British Pharmacopoeia and the results being statistically evaluated. Received September 26, 2000. Revision March 25, 2001.     

Bromatometric assay of simvastatin in pharmaceuticals

Titrimetric and spectrophotometric methods are proposed for the determination of simvastatin (SMT) in bulk drug and in tablets. The methods employ bromate-bromide mixture in acid medium as the brominating agent and iron (III) and thiocyanate as auxiliary regents. In titrimetry, SMT is treated with a measured excess of bromate-bromide mixture in HCl medium, and after a definite time, the unreacted bromine is determined iodometrically. In spectrophotometric method, the residual bromine is reduced by iron (II) and the resulting iron (III) is complexed with thiocyanate, and the absorbance is measured at 470 nm. In both methods, the amount of in situ generated bromine corresponds to the SMT content. The experimental conditions are optimized. Titrimetry is applicable over 1–10 mg range and the calculations are based on the molar ratio of 1: 0.666 (SMT: KBrO3). In spectrophotometric method, Beer’s law is obeyed over the concentration range 1–10 µg/mL. The calculated molar absorptivity is 3.02 × 10⁴ L/mol cm and the corresponding sandel sensitivity being 0.0081 µg/cm². The limit of detection (LOD) and limit of quantification (LOQ) are calculated to be 0.10 and 0.31 µg/mL, respectively. The intra-day and inter-day precision calculated from the analysis of pure SMT were less than 2 and 2.7%, respectively. The methods were satisfactorily applied to the determination of SMT in tablets, and no interferences from common tablet excipients were observed. The validity of the methods was further ascertained by parallel assay by an established technique and by recovery studies.     

Use of a diazocoupling reaction for sensitive and selective spectrophotometeric determination of furosemide in spiked human urine and pharmaceuticals

Two simple, sensitive, and selective spectrophotometric methods for the determination of 5-(aminosulfonyl)-4-chloro-2-((2-furanylmethyl)amino)benzoic acid (furosemide, FUR) are described. The methods are based on acid hydrolysis of FUR to free primary aromatic amine and diazotization followed by coupling with N-1-napthylethylene diamine (NEDA) (method A) or 4,5-dihydroxynaphthalene-2,7-disulfonic acid (chromotropic acid, CTA) (method B). The colored reaction product can be measured spectrophotometrically at 520 nm (method A) or 500 nm (method B). Beer’s law is obeyed over the ranges of 1.75–21.0 μg mL⁻¹ and 2.5–30.0 μg mL⁻¹, for method A and method B, respectively. Apparent molar absorptivities and Sandell’s sensitivities (in L mol⁻¹ cm⁻¹ and μg cm⁻² per 0.001 absorbance unit, respectively) were 1.34 × 10⁴ and 0.0253 using NEDA as the coupling agent, and 8.5 × 10³ and 0.0389 using CTA for the same purpose. Analysis of solutions containing seven different concentrations of FUR gave a correlation coefficient of 0.9979 using NEDA and 0.9984 using CTA, while the slope and the correlation coefficient of the regression equation were calculated. The reaction stoichiometry in both methods was evaluated by the limiting logarithmic method and was found to be 1: 1 (diazotized FUR: NEDA or diazotized FUR: CTA). The methods were successfully applied to the determination of FUR in spiked human urine and in pharmaceutical formulations. The recovery of FUR from spiked urine was satisfactory resulting in the values of (109.4 ± 4.37) % using NEDA and (113.0 ± 4.74) % using CTA. Results of the analysis of pharmaceuticals demonstrated that the proposed procedures are at least as accurate and precise as the official method while a statistical analysis indicated that there was no significant difference between the results obtained by the proposed methods and those of the official method.     

Determination of Solifenacin Succinate in Pure and Pharmaceutical Dosage forms by Spectrophotometry

Journal of Analytical Chemistry - Four simple, precise and sensitive visible spectrophotometric methods were developed for the determination of solifenacin succinate in pure and pharmaceutical...